Cementite decomposition in 100Cr6 bearing steel during high-pressure torsion: Influence of precipitate composition, size, morphology and matrix hardness

Premature failure of rail and bearing steels by White-Etching-Cracks leads to severe economic losses. This failure mechanism is associated with microstructure decomposition via local severe plastic deformation. The decomposition of cementite plays a key role. Due to the high hardness of this phase, it is the most difficult obstacle to overcome in the decaying microstructure. Understanding the mechanisms of carbide decomposition is essential for designing damage-resistant steels for industrial applications. We investigate cementite decomposition in the bearing steel 100Cr6 (AISI 52100) upon exposure to high-pressure torsion (maximum shear strain, Ƴmax = 50.2). Following-up on our earlier work on cementite decomposition in hardened 100Cr6 steel (Qin et al., Act. Mater. 2020 [1]), we now apply a modified heat treatment to generate a soft-annealed microstructure where spherical and lamellar cementite precipitates are embedded in a ferritic matrix. These two precipitate types differ in morphology (spherical vs. lamellar), size (spherical: 100–1000 nm diameter, lamellar: 40–100 nm thickness) and composition (Cr and Mn partitioning). We unravel the correlation between cementite type and its resistance to decomposition using multi-scale chemical and structural characterization techniques. Upon high-pressure torsion, the spherical cementite precipitates did not decompose, but the larger spherical precipitates (≥ 1 μm) deformed. In contrast, the lamellar cementite precipitates underwent thinning followed by decomposition and dissolution. Moreover, the decomposition behavior of cementite precipitates is affected by the type of matrix microstructure. We conclude that the cementite size and morphology, as well as the matrix mechanical properties are the predominating factors influencing the decomposition behavior of cementite. The compositional effects of Cr and Mn on cementite stability calculated by complementary density functional theory (DFT) calculations are minor in the current scenario. © 2021 Elsevier B.V

Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis.

Tertiary lymphoid organs emerge in tissues in response to nonresolving inflammation. Recent research characterized artery tertiary lymphoid organs in the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis-associated lymphocyte aggregates are organized into distinct compartments, including separate T-cell areas harboring conventional, monocyte-derived, lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors and memory cells; B-cell follicles containing follicular dendritic cells in activated germinal centers; and peripheral niches of plasma cells. Artery tertiary lymphoid organs show marked neoangiogenesis, aberrant lymphangiogenesis, and extensive induction of high endothelial venules. Moreover, newly formed lymph node-like conduits connect the external lamina with high endothelial venules in T-cell areas and also extend into germinal centers. Mouse artery tertiary lymphoid organs recruit large numbers of naïve T cells and harbor lymphocyte subsets with opposing activities, including CD4(+) and CD8(+) effector and memory T cells, natural and induced CD4(+) regulatory T cells, and memory B cells at different stages of differentiation. These data suggest that artery tertiary lymphoid organs participate in primary immune responses and organize T- and B-cell autoimmune responses in advanced atherosclerosis. In this review, we discuss the novel concept that pro- and antiatherogenic immune responses toward unknown arterial wall-derived autoantigens may be organized by artery tertiary lymphoid organs and that disruption of the balance between pro- and antiatherogenic immune cell subsets may trigger clinically overt atherosclerosis

Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked to Human Coronary Atherosclerosis

RATIONALE:B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining the BM B-1a population remain unexplored. CXCR4 (C-X-C motif chemokine receptor 4) has been implicated in human cardiovascular disease and B-cell homeostasis, yet the role of B-1 cell CXCR4 in regulating atheroprotective IgM levels and human cardiovascular disease is unknown. OBJECTIVE:To characterize the BM B-1a IgM repertoire and to determine whether CXCR4 regulates B-1 production of atheroprotective IgM in mice and humans. METHODS AND RESULTS:Single-cell sequencing demonstrated that BM B-1a cells from aged ApoE-/- mice with established atherosclerosis express a unique repertoire of IgM antibodies containing increased nontemplate-encoded nucleotide additions and a greater frequency of unique heavy chain complementarity determining region 3 sequences compared with peritoneal cavity B-1a cells. Some complementarity determining region 3 sequences were common to both compartments suggesting B-1a migration between compartments. Indeed, mature peritoneal cavity B-1a cells migrated to BM in a CXCR4-dependent manner. Furthermore, BM IgM production and plasma IgM levels were reduced in ApoE-/- mice with B-cell-specific knockout of CXCR4, and overexpression of CXCR4 on B-1a cells increased BM localization and plasma IgM against oxidation specific epitopes, including IgM specific for malondialdehyde-modified LDL (low-density lipoprotein). Finally, in a 50-subject human cohort, we find that CXCR4 expression on circulating human B-1 cells positively associates with plasma levels of IgM antibodies specific for malondialdehyde-modified LDL and inversely associates with human coronary artery plaque burden and necrosis. CONCLUSIONS:These data provide the first report of a unique BM B-1a cell IgM repertoire and identifies CXCR4 expression as a critical factor selectively governing BM B-1a localization and production of IgM against oxidation specific epitopes. That CXCR4 expression on human B-1 cells was greater in humans with low coronary artery plaque burden suggests a potential targeted approach for immune modulation to limit atherosclerosis

Development of Methods for Selective Gene Expression Profiling in Tertiary Lymphoid Structure Using Laser Capture Microdissection

Tertiary lymphoid structures (TLS) are de novo lymphoid formations that are induced within tissues during inflammatory episodes. TLS have been reported at various anatomic sites and in many different contexts like cancer, infections, autoimmunity, graft rejection, and idiopathic diseases. These inducible, ectopic, and transient lymphoid structures exhibit the prototypical architecture found within secondary lymphoid organs (SLO) and have been recently appreciated as a major driver of the local adaptive immune reaction. As TLS emerge within tissues, the isolation in situ and the molecular characterization of these structures are challenging to operate. Laser capture microdissection (LCM) is a powerful tool to isolate selective structural components and cells from frozen or paraffin-embedded tissues. We and other groups previously applied LCM to decipher the molecular network within TLS and uncover their intrinsic connection with the local microenvironment. In this chapter, we describe a detailed LCM method for selecting and isolating TLS in situ to perform comprehensive downstream molecular analyses